The first two-piece capsule was developed in 1848 and was made from animal-based gelatin, derived primarily from collagen. Capsules are now produced in hard and soft forms, and are common dosage forms for solid, semi-solid, liquid, pellet or herbal preparations primarily in the pharmaceutical and vitamin/health supplement markets. Capsules typically require fewer excipients to produce than tablet dosage forms, and consequently are easier to produce than tablets. They are also easy to swallow and are hence associated with patient compliance.
Currently, gelatin-based hard shell capsules make up a significant proportion of the global pharmaceutical market. Gelatin has high affinity for moisture and is known to react chemically with agents that contain functional groups, such as reducing functionalities (for example, aldehdye groups), which can make gelatin capsule unsuitable for certain drugs. Gelatin capsules are also sensitive to heat and humidity, which affect the usability of the product. Further, because gelatin is an animal-based product, some consumers seek to avoid gelatin-products for religious, cultural, or dietary restrictions, or even because of a perceived risk of contracting spongiform encephalopathy. The more common alternatives to gelatin based capsules are hydroxypropylmethylcellulose and starch capsules. However, these have shown erratic dissolution profiles.
Cellulose is a known natural biostable and biocompatible polymer material. Due to its safe biological characteristics, cellulose has been used in a number of applications. Cellulose has a high mechanical and wet strength, which makes it a good material for coatings, membranes, or barriers for intra-corporeal devices (e.g., surgical implants). While cellulose derivatives, such as hydroxypropylmethylcellulose, have been used to prepare capsules and some capsule-based delivery products, these cellulose derivatives are typically soluble in aqueous medium, and require addition of other formulation agents that increase manufacturing complexity and costs. [See, U.S. Pat. No. 6,752,953 (Chen, et al.); U.S. Pat. No. 2,526,683 (Murphy, et al.); U.S. Pat. No. 4,001,211 (Sarkar, et al.); U.S. Pat. No. 4,993,137 (Muto, et al.); U.S. Pat. No. 5,698,155 (Grosswald, et al.); U.S. Pat. No. 6,410,050 (Yang); and U.S. Pat. No. 5,756,123 (Yamamoto, et al.)].
Existing capsule-based delivery technology provides dosage forms with capsule shells that disintegrate or dissolve upon contact with an aqueous medium. Thus, the performance of capsules as an oral delivery system relies primarily upon the specific formulation of the active agent(s) or upon further capsule coating technology. Consequently, improperly formulated capsules can fail and cause undesired release of active agent(s) (e.g., high localized active agent concentrations), which can cause adverse physiological effects in the patient (e.g., GI irritation), or reduce the efficacy of the active agent(s) (e.g., hydrolyzable active agent(s)).
Existing capsule-based delivery technology does not by itself provide sustained- and/or controlled-release of active agents. Additional technology (e.g., coatings) must be used in combination with existing capsule shells in order to modify the inherent delivery profile of the encapsulated active agent(s).
Thus, there is a need to develop a capsule-based drug delivery system that provides good long-term storage stability, is chemically inert with the active agent(s) it contains, is relatively simple and economical to produce, and/or offers easy modifications of its drug release characteristics.